The therapeutic mechanism of antidepressant drugs is likely to include a circadian component. This possibility is being examined by testing in hamsters the effects of antidepressant and neuroleptic drugs on the state of the circadian pacemaker that controls daily rhythms of motor activity, temperature and EEG sleep. A recent line of investigation has explored the role of serotonin in modulating the circadian system response to light. VIP cells within the SCN are of interest for two reasons. First, the visual pathway for circadian entrainment, and a serotonergic pathway originating in the raphe nucleus, both project to these VIP cells. Second, VIP levels within the SCN exhibit seasonal variation as a result of changes in daylength. VIP cells may therefore be part of a seasonal mechanism that controls circadian variation in light responsiveness and behavior. The relationship between vasoactive intestinal peptide (VIP) containing cells, and serotonin levels within the suprachiasmatic nucleus (SCN) is being examined using immunohistochemical and image analysis techniques. We have found that chronic treatment with the antidepressant drug clorgyline elevates immunoreactivity to vasoactive intestinal peptide (VIP) throughout the rostral caudal extent of the SCN. The increase in VIP immunoreactivity is likely to be related to chronic elevation of serotonin within the SCN since serotonergic fibers project to VIP cells within the SCN. It is hypothesized that in seasonal depression, the behavioral effect on circadian rhythms (e.g. sleep-wakefulness) of serotonergic antidepressant drugs, is mediated by the drug effect on VIP cells within the SCN.